title: SOCS1 regulates type I/type II NKT cell balance by regulating IFNgamma signaling.
abstract: Suppressor of cytokine signaling-1 (SOCS1) has been shown to be an essential negative regulator of cytokine responses, including those of IFNγ, IL-2, IL-4 and IL-7. SOCS1 deficiency resulted in hyperactivation not only of T cells in general but also of NKT cells specifically. Consistent with previous reports, T- and NKT-cell-specific deletion of Socs1 in mice resulted in enhanced sensitivity to ConA-induced hepatitis. Compared with wild-type (WT) NKT cells, SOCS1-deficient NKT cells produced larger quantities of IFNγ in response to ConA and proliferated faster in response to IL-2 and IL-15. To our surprise, however, SOCS1-deficient NKT cells did not respond to the synthetic glycolipid ligand alpha-galactosylceramide (α-GalCer), though they did respond to sulfatide. α-GalCer-CD1d-tetramer-positive type I NKT [invariant NKT (iNKT)] cells were marginally detected in the periphery of SOCS1-conditional knockout (cKO) mice, suggesting that most of the SOCS1-deficient NKT cells at the periphery were type II NKT cells. Consistently, invariant Vα14 expression was much lower in SOCS1-deficient NKT cells than in WT NKT cells, indicating that iNKT cell homeostasis was abnormal in SOCS1-cKO mice. This reduction in iNKT cells was not observed in mice of an IFNγ-deficient background. These results suggest that SOCS1 is an important regulator of the balance between type I and type II NKT cells at the periphery.
authors.affiliation: Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Hiwatashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Ichiyama
authors.forename: Rimpei
authors.initials: R
authors.lastname: Morita
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekiya
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kimura
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Sibata
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Kuroda
authors.forename: Reiko
authors.initials: R
authors.lastname: Takahashi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation; D003208:Concanavalin A / Q000494:pharmacology; D006520:Hepatitis, Animal / Q000139:chemically induced / Q000401:mortality / Q000473:pathology; D007371:Interferon-gamma / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008934:Mitogens / Q000494:pharmacology; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis
chemical_list: D008934:Mitogens; D050826:Suppressor of Cytokine Signaling Proteins; D003208:Concanavalin A; D007371:Interferon-gamma